Thyroid hormone is not required for the initiation of brain myelin basic protein (MBP) gene expression which occurs on the 4th postnatal day in mice. MBP mRNA encoding all four major MBP isoforms are detected on that day in the absence of thyroid hormone. Hypothyroidism results in a 3- to 4-fold decrease in total MBP A concentration in newborn mice. Among the isoforms, all of which are decreased by hypothyroidism, the greatest decrease (9- and 17-fold, respectively) is seen in mRNA encoding 21.5 and 18.5 kDa MBP on the 18th postnatal day, when these isoforms are maximally expressed. At other times and for other isoforms the decrease ranges from 2- to 4-fold. MBP mRNA in the brain of adult mice and rats rendered hypothyroid at 5 weeks of age and killed 4 weeks later is decreased to 4 fold. This indicates that hypothyroidism still affects MBP gene O-expression in young adults (at about the time of sexual maturity). In rats thyroidectomized at 10 weeks of age, hypothyroidism has no effect. Thyroxine treatment reverses the effect of hypothyroidism in young adults, but excess thyroxine administration for 12 days does not alter MBP mRNA levels. The manuscript describing this study has been prepared for publication.